Autonomic cardiac control. I. Estimation and validation from pharmacological blockades

Pharmacological blockades have been used to estimate the relative contributions of the autonomic branches to cardiac chronotropic control. Systematic biases in these estimates, however, can arise from both methodological and physiological factors. Selective blockades can be interpreted by two inferential models, and a single blockade condition can yield estimates of autonomic control for both autonomic branches. The residual autonomic control of the heart after blockade of a single division provides an index of the functional contribution of the unblocked branch. In contrast, the change in chronotropic state of the heart after blockade of the same division reflects the subtractive loss of that branch and thus provides an index of the normal contribution of the blocked branch. We demonstrate that the systematic biases that can arise in blockade studies introduce distortions of the subtractive and residual estimates that are of equal magnitude but opposite sign. Consequently, the discrepancy between the subtractive- and residual-model estimates provides a measure of bias in blockade studies and permits the derivation of validity indices that can facilitate interpretations of blockade data.